NEW STABLE FORMULATIONS OF 1-Z-BROMOALK-1-ENE COMPOUNDS AND USE THEREOF IN THE MANUFACTURE OF PHEROMONES

Abstract

The present invention concerns new stable compositions of 1-Z-bromoalk-1-ene compounds of general formula (A). These compositions are characterized in that they also comprise either at least one cyclic ether compound comprising between 4 and 6 carbon atoms, or at least one ether of general formula (B) in which R.sub.1 and R.sub.2 are identical or different and selected from the group consisting of: a linear or branched alkyl group containing 1 to 8 carbon atoms.

Claims

1-9. (Canceled)

10. A composition comprising: - a 1-Z-bromoalk-l-ene of general formula A: ##STR00011## wherein R is a linear alkyl group having from 1 to 24 carbon atoms; and - an ether which is: either a cyclic ether having a ring comprising from 4 to 6 carbon atoms, optionally substituted by a C1-C3 alkyl group, or an ether of general formula B: ##STR00012## wherein n is from 1 to 4; m is from 0 to 5; and R.sub.1 and R.sub.2, identical or different, are selected from the group consisting of a linear or branched alkyl group having from 1 to 8 carbon atoms; wherein the 1-Z-bromoalk-1-ene has a content in the composition from 70 to 99.5% by weight based on the total weight of the composition.

11. The composition according to claim 10, wherein the cyclic ether has a ring comprising from 4 to 6 carbon atoms, optionally substituted by a methyl.

12. The composition according to claim 10, wherein m is from 1 to 3.

13. The composition according to claim 10, wherein the content of 1-Z-bromoalk-1-ene in the composition is from 90 to 99% by weight based on the total weight of the composition.

14. The composition according to claim 10, wherein the content of 1-Z-bromoalk-1-ene in the composition is from 93 to 98% by weight based on the total weight of the composition.

15. The composition according to claim 10, wherein R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decanyl, undecanyl, dodecanyl, tridecanyl, tetradecanyl, pentadecanyl, hexadecanyl, heptadecanyl and octadecanyl.

16. The composition according to claim 10, wherein R.sub.2 and R.sub.2, identical or different, are selected from the group consisting of methyl, ethyl, isopropyl, tert-butyl and neopentyl.

17. The composition according to claim 10, wherein the cyclic ether is selected from the group consisting of tetrahydrofuran, methyl tetrahydrofuran and dioxane.

18. The composition according to claim 10, wherein the ether has a content in the composition from 0.5 to 30% by weight based on the total weight of said composition.

19. The composition according to claim 10, wherein the ether has a content in the composition from 1 to 10% by weight based on the total weight of said composition.

20. The composition according to claim 10, wherein the ether has a content in the composition from 3 to 10% by weight based on the total weight of said composition.

21. A method for coupling a compound of general formula A: ##STR00013## wherein R is a linear alkyl group having from 1 to 24 carbon atoms, with a compound selected from the group consisting of organomagnesiums and organolithiums, comprising reacting a composition according to claim 10 with the compound selected from the group consisting of organomagnesiums and organolithiums.

22. The method according to claim 21, wherein the compound selected from the group consisting of organomagnesiums and organolithiums is an organomagnesium compound of general formula Y—(CH2)n—MgX, wherein n is an integer from 2 to 20; X is a chlorine or bromine atom; and Y is an ether function; ##STR00014## or an alcoholate function selected from the group consisting of —OMgX,—OC(O)CH.sub.3, with R.sub.3 and R.sub.4, identical or different, being a C1-C8 alkyl.

23. The method according to claim 22, wherein R3 and R4, identical or different, are selected from the group consisting of methyl, ethyl and propyl.

24. The method according to claim 21, wherein the compound selected from the group consisting of organomagnesiums and organolithiums is an organolithium compound of general formula. Y-(CH.sub.2).sub.n-Li, wherein n is an integer from 2 to 20, and Y is an alcoholate function selected from e group ##STR00015## consisting of —OLi, —OC(O)CH.sub.3, with R3 and R4, identical or different, being a C1-C8

25. The method according to claim 24, wherein R3 and R4, identical or different, are selected from the group consisting of methyl, ethyl and propyl.

26. The method according to claim 21, wherein coupling of the compound of general formula A with the compound selected from the group consisting of organomagnesiums and organolithiums leads to manufacturing a fatty chain pheromone.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0032] In the sense of the present invention, “storage medium which is compatible with subsequent reaction with an organomagnesium or organolithium” means a storage medium in which only the 1-Z-bromoalk-1-ene compound(s) of general formula A is (are) capable of reacting with organomagnesiums or organolithiums.

[0033] In the sense of the present invention, “organomagnesium” means an organic compound having a carbon-magnesium bond. The family of organomagnesium compounds includes, but is not limited to, the Grignard reagents, which are mixed organomagnesium compounds of formula R′-MgX, where R′ is a carbon chain and X is a halogen, and in particular the compounds of general formula Y—(CH.sub.2).sub.n—MgX, where n is an integer comprised between 2 and 20, preferably n is comprised between 6 and 12, and where Y is an ether, alcoholate (—OMgX), acetylate (—OC(O)CH3) or acetal function (

##STR00005##

[0034] with R3 and R4 being C1-8 alkyl chains, identical or different, preferably R3 and R4 are selected from methyl, ethyl or propyl groups).

[0035] In the sense of the present invention, “organolithium” means an organometallic compound having a carbon-lithium bond. Organolithium compounds include, but are not limited to, lithium alkyls such as methyllithium, butyllithium or hexyllithium or compounds of general formula R″-Li, where R″ is a carbon chain, and in particular the compounds of general formula Y-(CH.sub.2).sub.n-Li where n is an integer comprised between 2 and 20, preferably n is comprised between 6 and 12, and where Y is an ether, alcoholate (—OLi), acetylate (—OCCH.sub.3) or acetal function

##STR00006##

[0036] with R3, R4 C1-C8 alkyl chains, identical or different, preferably selected from methyl, ethyl or propyl groups).

[0037] In the sense of the present invention, “labile hydrogen” means a hydrogen atom having an acidic character such as, for example, but not limited to, the hydrogen of alcohols, carboxylic acids, amines, and primary and secondary amides. Thus, an ether that does not include labile hydrogen is unlikely to generate protons.

[0038] A first object of the present invention is a composition comprising: [0039] a 1-Z-bromo-alk-1-ene of general formula A:

##STR00007##

[0040] where R is a linear alkyl group having between 1 and 24 carbon atoms; and [0041] either at least one cyclic ether whose ring comprises between 4 and 6 carbon atoms, optionally substituted by a C1-C3 alkyl group, preferably by a methyl; [0042] or at least one ether of general formula B:

##STR00008##

[0043] where n is comprised between 1 and 4 and m is comprised between 0 and 5, in particular between 1 and 5, preferably m is comprised between 1 and 3; and R1 and R2, identical or different, are selected from the group comprising: a linear or branched alkyl group having 1 to 8 carbon atoms.

[0044] According to a preferred embodiment, the cyclic ether is selected from tetrahydrofuran, methyl tetrahydrofuran and dioxane.

[0045] According to an embodiment, the group R of the compound of general formula A is selected from the group comprising methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decanyl, undecanyl, dodecanyl, tridecanyl, tetradecanyl, pentadecanyl, hexadecanyl, heptadecanyl and octadecanyl groups.

[0046] According to an embodiment, the groups R1 and R2 of the compound of general formula B, identical or different, are selected from the group comprising methyl, ethyl, isopropyl, tert-butyl and neopentyl groups. Advantageously, the compound B is methyl tert-butyl ether. According to an embodiment, the 1-Z-bromoalk-1-ene content in the composition according to the invention is comprised between 70 and 99.5% by weight, preferably between 90 and 99% by weight and still more preferentially between 93 and 98% by weight, based on the total weight of said composition.

[0047] According to an embodiment, the ether content in the composition according to the invention is comprised between 0.5 and 30% by weight, preferably between 1 and 10% by weight and still more preferentially between 3 and 10% by weight, based on the total weight of said composition.

[0048] A second object of the present invention is the use of the composition according to the invention in a coupling reaction of a compound of general formula A with a compound selected from the group comprising organomagnesiums and organolithiums.

[0049] According to an embodiment, the invention relates to the use of the composition according to the invention in a coupling reaction of a compound of general formula A with an organomagnesium compound of formula R′-MgX, wherein R′ is a carbon chain and X is a halogen. According to a preferred embodiment, said organomagnesium compound has the general formula Y-(CH.sub.2).sub.n-MgX where n is an integer comprised between 2 and 20, preferably n is comprised between 6 and 12, and where X is a chlorine or bromine atom and where Y is an ether, alcoolate (—OMgX), acetylate (—OC(O)CH3) or acetal function (

##STR00009##

[0050] with R3 and R4 being C1-C8 alkyl chains, identical or different, preferably R3 and R4 are selected from methyl, ethyl and propyl groups). Preferably, the reaction takes place in the presence of a catalyst. According to another embodiment, the invention relates to the use of the composition according to the invention in a coupling reaction of a compound of general formula A with an organolithium compound of general formula Y-(CH.sub.2).sub.n-Li where n is an integer comprised between 2 and 20, preferably n is comprised between 6 and 12, and where Y is an ether, alcoholate (—OLi), acetylate (—OC())CH.sub.3) or acetal function (

##STR00010##

[0051] with R3 and R4 being C1-C8 alkyl chains, identical or different, preferably R3 and R4 are selected from methyl, ethyl and propyl groups). Preferably, the reaction takes place in the presence of a catalyst. A third object of the present invention is the use of a composition according to the invention for the manufacture of fatty chain pheromone.

[0052] According to an embodiment, the invention relates to the use of the composition according to the invention for the manufacture of lepidopteran pheromone carrying at least one unsaturation in a Z-configuration via a coupling reaction in the presence of an organomagnesium or an organolithium and a metal complex. According to an embodiment, the compositions according to the invention are used for the synthesis of compounds selected from: Z-7-decen-1-yl acetate, Z-9-dodecen-1-yl acetate, Z-9-dodecen-1-ol, Z-11-tetradecen-1-ol, Z-11-tetradecen-1-ol, Z-11-tetradecen-1-yl acetate, Z-11-tetra-decenal, (Z)-hexadec-13-en-11-yn-1-yl acetate, (Z,Z)-11,13-hexadecadien-1-yl-acetate and (Z,Z)-11,13-hexadecadienal. According to an embodiment, the compositions according to the invention are used for the synthesis of compounds selected from: Z-5-decen-1-ol, Z-5-decen-1-yl acetate, Z-7-dodecen-1-ol, Z-7-dodecen-1-yl acetate, Z-9-tetradecen-1-ol, Z-9-tetradecen-1-yl acetate, Z-9-tetradecenal, Z-11-hexadecen-1-ol, Z-11-hexadecen-1-yl acetate, Z-11-hexadecenal, Z-13-octadecen-1-yl acetate and Z-13-octadecenal. The following examples are intended to illustrate the present invention in a non-limiting manner and will provide a better understanding of the invention and its scope.

EXAMPLES

[0053] The synthesis of the precursor α,β-di-bromo acids of the compounds according to the invention are obtained according to the procedure described in the publication K. Mori, J.-L. Brevet, Synthesis, 1991, 1125.

[0054] The analytical method consists of gas chromatography (GC) analysis on an HP 5890 Series II instrument. The chromatographic column is an Optima delta 6.30 μm, 0.25 mm, 0.25 μm column.

[0055] The oven follows the following temperature profile: Initial temperature: 40° C., Initial time 5 min; Gradient 5° /min, Final temperature: 125° C., Duration 15 min. The injector temperature is 250° C., the detector temperature is 280° C., the injected volume is 1 μL and the pressure is 6 psi. The sample concentration is 75 g/L in tetrahydrofuran (THF).

[0056] The reactions are carried out in a 20 L jacketed glass reactor and the distillations are carried out using a glass column with 10 theoretical trays.

Example 1: Preparation of 1-Z-bromobut-1-ene

[0057] In a clean reactor previously purged with nitrogen, the following are successively introduced: [0058] 2,3-dibromopentanoic acid: 3.830 kg with a mass purity of 86.6% (1 eq); and [0059] dimethylformamide (DMF): 7.660 L (2 vol). [0060] The coolant is cooled to -15° C. The solution is then heated to 55° C., then an aqueous solution of 50 wt.% of soda is added at a rate that controls the CO.sub.2 produced by the decarboxylation reaction and maintains the temperature of the reaction medium between 53° and 80° C. [0061] At the end of the addition of the aqueous solution with 50 wt.% of soda, the temperature of the reactor is increased to 110° C., first under atmospheric pressure, then under reduced pressure at 100 mbar so as to remove the water and the last traces of product.

[0062] The good distillation fractions are then collected and the organic solvent (DMF) is removed by water wash.

[0063] 1-Z-Bromobut-1-ene (1.414 kg) with an isomer excess of 99.8/0.2 and a mass purity >99% is obtained. The water content measured by Karl Fischer titration is less than 0.15%.

Example 2: Preparation of 1-Z-bromohex-1-ene

[0064] In a clean reactor previously purged with nitrogen, the following are successively introduced: [0065] 2,3-dibromoheptanoic acid: 3.5 kg with a mass purity of 88% (1 eq); and [0066] dimethylformamide (DMF): 6.3 L (2 vol)

[0067] The coolant is cooled to -15° C.

[0068] The solution is then heated to 55° C., then an aqueous solution of 50 wt.% of soda is added at a rate that allows the CO.sub.2 produced by the decarboxylation reaction to be controlled and the temperature of the reaction medium to be maintained between 53° and 80° C.

[0069] At the end of the addition of the aqueous solution with 50 wt.% of soda, the temperature of the reactor is increased to 110° C., first under atmospheric pressure, then under reduced pressure at 100 mbar so as to remove the water and the last traces of product.

[0070] The good distillation fractions are then collected and the organic solvent (DMF) is removed by water wash.

[0071] 1-Z-Bromohex-1-ene (1.175 kg) is obtained with an isomer excess of 99.7/0.3 and a mass purity >99%.

Example 3: Preparation of compositions according to the invention

[0072] A proportion (in %) of an ether is added to the 1-Z-bromobut-1-ene of Example 1 (denoted C4) or to the 1-Z-bromohex-1-ene of Example 2 (denoted C6), and the stability of the Z/E ratio is studied by considering the number of days from which the Z/E ratio reaches a level of less than 95% of the Z isomer under temperature-controlled aging conditions (denoted T95). The data on the studied compositions are collected in the following table:

TABLE-US-00001 TABLE 1 Formulation no. 1 2 3 4 5 6 7 8 9 10 Bromoalkene C4 C6 Ether added none THF MTBE MTBE MTBE None THF MTBE MTBE MTBE Weight % of 0 5 3 4.5 9 0 5 3 4 9 ether Initial Z/E 97.1/2.9 99.8/0.2 99.7/0.3 ratio Storage 4 25 25 25 4 4 25 25 25 4 temperature (° C.) T95 (days) 3 >85 >285 160 >203 20 >85 >85 >85 >85 MTBE = methyl tert-butyl ether

[0073] The inventors have thus demonstrated that the ether-free compositions exhibit an isomer ratio which goes from 97.1/2.9 to 95/5 at 4° C. in 3 days in the case of 1-Z-bromobut-1-ene and from 99.7/0.3 to 95/5 at 4° C. in 20 days in the case of 1-Z-bromohex-1-ene. On the other hand, all the compositions having even a limited proportion of an ether lead to stereochemical stabilities over durations of more than 30 days at 25° C., which makes them suitable for use in a multi-step synthesis process. The THF and MTBE selected for this example are conventional solvents for making or using organomagnesiums or organolithiums.

[0074] Example 4: Preparation and stability of compositions outside the invention

[0075] Either 5% of an alkene type solvent (amylene), or toluene, or a chlorinated solvent (dichloromethane) is added to the 1-Z-bromobut-1-ene of Example 1. In the case of compositions comprising the alkene (amylene) type solvent or toluene, the T95s are 9 and 10 days respectively. In the case of the composition comprising the chlorinated solvent (dichloromethane), the T95 is higher than 20 days but the introduced dichloromethane reacts violently with the organolithiums and organomagnesiums.

[0076] Example 5: Use of Composition 9 of Example 3 in reaction with BrMgO-(CH.sub.2).sub.10-MgBr for the manufacture of Z-11-hexadecenol

[0077] A 1 mol/L solution (44 mL) of the organomagnesium BrMgO-(CH.sub.2).sub.10-MgBr obtained from chlorodecanol is introduced under argon at 25° C. into a dry 250 mL four-necked round-bottom flask equipped with a thermometer and mechanical stirring. Then 45 mL of THF is added. The mixture is cooled to -5° C. One portion (14 mg) of iron(III) acetylacetonate is added. The walls of the four-necked round-bottom flask are rinsed with 4 mL THF. (Z)-Bromohex-1-ene (6.52 g) is then introduced over 5 minutes while maintaining a temperature comprised between —5° C. and 0° C. Stirring is maintained at this temperature for 20 minutes.

[0078] A 1 mol/L HCl solution (80 mL) is added while keeping the temperature below 30° C. The two phases obtained are separated: the aqueous phase is extracted with 3×20 mL petroleum ether; the organic phases are combined, dried over MgSO4, filtered and concentrated on a rotary evaporator. The residual oil is distilled under vacuum. Boiling temperature at 0.04 mmHg =118° C. A colorless oil (8.6 g) composed of a mixture of the Z and E isomers of 11-hexadecenol (89% yield) with a Z/E isomer ratio of 97/3 is then obtained.

[0079] Example 6: Use of Composition 5 of Example 3 for the synthesis of pine processionary pheromone ((Z)-hexadec-13-en-11-yn-1-yl acetate)

[0080] Diethylamine (35 mL) is loaded (temperature: 19° C., colorless medium) into a 250 mL triple-necked round-bottom flask equipped with magnetic stirring, at room temperature, and then the reaction medium is inerted by a vacuum/nitrogen sequence. [0081] 10 mL of previously inerted diethylamine is taken to solubilize 10 g of 11-dodecynol. [0082] 20 mg of PdCl2 (orange medium) and 54 mg of CuCI (blue/violet medium) are then added to the triple-necked round-bottom flask. After the medium is homogenized, a vacuum/nitrogen inerting is carried out (the medium becomes green, small endotherm of 5° C.). [0083] 9.7 g of 1-bromobut-1-ene solution having 9% of THF is introduced dropwise into the medium. [0084] The docec-11-yn-1-ol in solution in diethylamine is then added dropwise. [0085] Stirring is maintained at 60° C. for 5 h until the medium turns light brown.

[0086] At the end of the reaction, 50 mL of 0.1 N hydrochloric acid solution is added and then several extractions with methyl cyclohexane are performed. After evaporation of this solvent 12.6 g of 97% (Z)-hexadec-13-en-11-yn-1-yl acetate with a Z/E isomer ratio of 98/2 is obtained.